Prostatic cancer is the most common non-skin infectious malignant tumors, and is the second leading cause of death in males, second to lung cancer. In United States, near 190 thousand of people are diagnosed as suffering prostatic cancer each year, in which approximately 31 thousand of people die from it. Prostatic cancer is a multifocal disease, so that the whole gland should be managed and treated. At present, the treatment methods mainly include observation only (intimate observation and wait), operation (radical prostatectomy), radiation (external irradiation or brachytherapy using an implanted radioactive source), radiation together with hormonotherapy (new adjuvant therapy) and hormone therapy (androgen-blocking therapy). Furthermore, it has been reported that cryotherapy, chemotherapy and other novel methods are also used for a local lesion by some doctors. Unfortunately, however, there are some disadvantages in all these methods, so that novel treatment methods are urgently demanded for prostatic cancer.
It has been demonstrated by clinical studies that photodynamics therapy (PDT) is an attractive form for cancer treatment, the principle of which includes: a photosensitizer is selectively absorbed by the tumor tissue and stored inside, and subsequently the photosensitizer is activated under local irradiation using the light at an appropriate wavelength, so that photosensitive effect is created. There will not be severe systemic side effect resulted from PDT, and it can be used repeatedly. PDT will not affect the tissue cells around when it destroys the tumor cells. There are 3 prominent advantages of PDT, including: favorable acceptability, low side effect and high efficiency.
At the end of 1970s and the early of 1990s, many attempts have been made by scientists to obtain a photosensitizer-PDT for prostatic cancer, so that the tissue-based photosensitizer has been developed. Meanwhile, novel PDT-mediated photosensitizer appears to have a great potential for the treatment of prostatic cancer (Photodynamic Therapy: A New Approach to Prostate Cancer. Curr. Urol. Rep. 2003, 4, 221-228). It has been proved by the University College London (London, UK) that there was a potential therapeutic effect of temoporfin for the treatment of prostatic cancer. Zaak and his colleagues reported the use of aminolevulinic acid-mediated protoporphyrin IX for the treatment of prostatic cancer (Photodynamic therapy by means of 5-ALA induced PPIX in human prostate cancer—preliminary results. Medical Laser Application 2003, 18, 91-95). Motexafin lutetium is a remarkable vessel activating photosensitizer, and has been tested in dog model (Photodynamic therapy in the canine prostate using motexafin lutetium. Clin Cancer Res 2001, 7, 651-660), Motexafin lutetium has also been applied to the patient after radiotherapy. It has been reported that it is better to use high dose PDT than low dose PDT. Padoporfin (Tookad®) and padeliporfin (Stakel®) are palladium-bacteriopheophorbide photosensitizer. On the first test stage of Padoporfin, 28 Canada patients suffered from periodic prostate cancer were enrolled for radiotherapy. It has been indicated that the pharmacuetical dosage of 2 mg/kg has the best therapeutic effect. Subsequently, the effect of using padeliporfin in the treatment of prostatic cancer of male patients without radiotherapy is also quite favorable. In conclusion, since the first use of photodynamics therapy for the treatment of prostatic cancer in 1978 (Photoradiation Therapy for the Treatment of Malignant Tumors. Cancer Res. 1978, 38, 2628-2635), and with the significant development of light transmission and photosensitizer design, many photosensitizers can be finally evaluated in formal clinical trials.
Although many photosensitizers have been developed in recent years and some were tested in clinical trials, such as Tookad and m-THPC, there are inherent disadvantages in these two analogues. For example, although no obvious skin phototoxicity induced by Tookad after long wavelength irradiation is observed, the therapeutic effect is not completely the same for all the patients, since the infusion and light process almost occur at the same time due to very short time span from the injection to the light process (i.e., very short effective treatment window). Additionally, after the injection of m-THPC, the medicine concentration will be adequate to kill tumor cells after a long period (3-4 days) of blood circulation; furthermore, it will also have severe skin phototoxicity.
There is another type of well-tested photosensitizer of tetrapyrrole or reduced tetrapyrrole structure, 2-((1′-n-hexyloxy)ethyl)-2-devinyl-pyropheophorbide-α (HPPH) and the analogues thereof, wherein the HPPH has the following structure:

The preparation method of HPPH and the salts thereof can be found in U.S. Pat. No. 5,198,460 (Publication No. RE39094) and U.S. Pat. No. 5,314,905 (Publication No. RE38994) or the following article: Methyl Pyropheophorbide-a Analogs: Potential Fluorescent Probes for the Peripheral-Type Benzodiazepine Receptor. Effect of Central Metal in Photosensitizing Efficacy. J. Med. Chem (rapid communication). 2005, 48 (11), 3692-3695. The phototoxicity duration of HPPH is much shorter than that of other photosensitizers, and HPPH has less damage to normal tissues with better therapeutic effect. However, erythema and other injuries will still be induced when tumor and other hyperplastic tissues are treated.
In another aspect, the key point in the use of photosensitizer-PDT therapy for the treatment of prostatic cancer is to enhance the selectivity of PDT photosensitive reagent to prostatic cancer cells. At present, in many cancer imaging and treatment methods, proliferation of tumor cells and DNA synthesis are utilized. The synthesis of deoxyribonucleic acid (DNA) occurs at a special stage—S phase in cell cycle. A great amount of DNA is synthesized during tumor cell proliferation, while thymidine kinase 1 has higher activity in hyperplastic cells, which is regulated by cells of S phase. Accordingly, the cell proliferation can be investigated by comparing the DNA synthesis of cells of stationary phase and hyperplastic cells of S phase in cell cycle via labeled thymidine. Early in laboratory, thymidine was labeled by 3H and 14C, and subsequently, 11C-thymidine was synthesized using positron emission tomography (PET). Pyrimidine is the basic unit for DNA synthesis, so that the use of 11C-thymidine for imaging is of great significance. Although this method is suitable for survey and effectiveness investigation, it is still not well acceptable due to excessively short half life of 11C. Since the half life of 11C-thymidine is very short and it may be degraded rapidly, the regular clinical application is not practical. As a result, efforts have been continuously made to find thymidine analogs with better imaging performance.
Thymidine analogs have been widely investigated as a possible therapeutic compound in both pharmaceutical industry and academic field. These analogs have been initially investigated by Dr. Charles Heidelberg. He tried to find a thymidine analog that can interfere the synthesis of DNA, and 5-fluorouracil was finally developed in 1975. 5-fluorouracil is a very effective antineoplastic drug, and still extensively employed in clinical treatment. When the thymidine analog 18F-FLT enters inside of the body, it can be absorbed by cells and aggregated after phosphorylation by thymidine kinase 1. It has been found that 3′-deoxy-3′-fluorothymidine (FLT) can be labeled by 18F (18FLT), an isotope with longer half-life (109.8 min). By evaluation of the performance of many nucleoside analogs for the imaging of hyperplasia, 18F-FLT (3′-deoxy-3′-fluorothymidine) is still the best method by far.
Furthermore, when prostatic cancer is treated by photosensitizer-PDT therapy, the whole prostate is demanded to be exposed under illumination at appropriate wavelength (based on the photosensitizer used). In addition, although photosensitizer-PDT therapy is very effective for cancer treatment, it only can be used for local treatment, i.e., for primary tumor, and it has limited application in the treatment of metastatic tumor. For metastatic tumors, chemotherapeutic agents are commonly needed, such as paclitaxel, which has systemic effectiveness. Accordingly, it is limited, at present, to use photosensitizer-PDT therapy or chemotherapy alone for the treatment of prostatic cancer, which has undesirable effect.